ABSTRACT
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.
Subject(s)
COVID-19/therapy , Drug Delivery Systems/methods , Nanoparticles/administration & dosage , RNA, Small Interfering/administration & dosage , RNAi Therapeutics/methods , Animals , COVID-19/epidemiology , COVID-19/virology , Humans , Models, Genetic , Nanoparticles/chemistry , Pandemics/prevention & control , RNA, Small Interfering/chemistry , RNA, Small Interfering/genetics , SARS-CoV-2/physiologySubject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Vaccines, Synthetic/immunology , Vaccinology/trends , Animals , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Device Approval/legislation & jurisprudence , Germany , HIV Infections/immunology , HIV Infections/prevention & control , Humans , Immunization Schedule , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Malaria/immunology , Malaria/prevention & control , Mice , Nanoparticles/administration & dosage , Nanoparticles/chemistry , RNAi Therapeutics/methods , Rats , SARS-CoV-2/immunology , Time Factors , Tuberculosis/immunology , Tuberculosis/prevention & control , United States , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effectsABSTRACT
After the increasing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections all over the world, researchers and clinicians are struggling to find a vaccine or innovative therapeutic strategies to treat this viral infection. The severe acute respiratory syndrome coronavirus infection that occurred in 2002, Middle East respiratory syndrome (MERS) and other more common infectious diseases such as hepatitis C virus, led to the discovery of many RNA-based drugs. Among them, siRNAs and antisense locked nucleic acids have been demonstrated to have effective antiviral effects both in animal models and humans. Owing to the high genomic homology of SARS-CoV-2 and severe acute respiratory syndrome coronavirus (80-82%) the use of these molecules could be employed successfully also to target this emerging coronavirus. Trying to translate this approach to treat COVID-19, we analyzed the common structural features of viral 5'UTR regions that can be targeted by noncoding RNAs and we also identified miRNAs binding sites suitable for designing RNA-based drugs to be employed successfully against SARS-CoV-2.